基于数据挖掘和网络药理学的中药治疗糖尿病大血管病变的用药规律及机制分析

Analysis of Medication Rules and Mechanisms of Chinese Medicinals in Treatment of Diabetic Macroangiopathy Based on Data Mining and Network Pharmacology

目的:基于数据挖掘和网络药理学挖掘并探讨防治糖尿病大血管病变中药新方的理论基础和潜在机制。方法:在中国知网、万方医学网、PubMed等数据库收集防治糖尿病大血管病变的临床处方,系统聚类分析药物之间的相似性或者相关性并进行分类,再根据专业知识选择相应类别,客观方法与主观能动相结合,故而运用SPSS Statistics 25.0软件进行系统聚类分析获得新方,继而在TCMSP和BATMAN-TCM数据库获得新方中药化学成分和靶点,在GeneCards、OMIM、DRUGBANK数据库获得糖尿病大血管病变的潜在靶点,利用韦恩图获取两者交集靶点,将交集靶点提交至STRING 11.0和Cytoscape 3.8.0制作核心靶点网络互作图,在DAVID数据库进行GO和KEGG富集分析。结果:新方组成以养阴生津之生地、玄参、麦冬为君,益气生津之黄芪、五味子为臣,并佐以活络化瘀之丹参、葛根,全方养阴益气生津,活血化瘀通络,标本兼顾,疾病痊愈,该方是从数据库众多方剂中按规律分析出来,配伍恰当,直指病机;其治疗糖尿病大血管病变的有效成分包括β-谷固醇、木犀草素、丹参酮IIA、槲皮素等;核心靶点有MAPK8、EDN1、EGF、STAT3、PRKCA、EGFR、RELA、VEGFA、IL-6、PIK3CA、AKT1、MAPK1、TNF等,信号通路主要有HIF-1、肿瘤坏死因子、FoxO、血管内皮生长因子等信号通路以及细胞凋亡和破骨细胞分化等。结论:本研究通过数据挖掘和网络药理学挖掘的中药新方可养阴益气、活络化瘀,改善糖尿病大血管病变气阴两虚和血脉瘀阻之病机,发挥调节糖脂代谢、改善胰岛素抵抗、减轻炎症和氧化应激反应等作用,继而达到防治糖尿病大血管病变的最终目的,以期为今后的实验研究和临床应用提供依据和思路。

Objective:To explore the theoretical basis and potential mechanisms of new Chinese medicinal prescriptions for the prevention and treatment of diabetic macroangiopathy based on data mining and network pharmacology.Methods:The clinical prescriptions for the prevention and treatment of diabetic macroangiopathy were retrieved from such databases as CNKI,Wanfang Data Knowledge Service Platform,and PubMed and then subjected to cluster analysis using SPSS Statistics 25.0.The chemical compositions and targets of Chinese medicinals in the new prescription yielded by cluster analysis were collected from TCMSP and BATMAN-TCM,and the potential targets of diabetic macroangiopathy from GeneCards,OMIM and DRUGBANK.The intersection targets between Chinese medicinals and diabetic macroangiopathy revealed by the Venn diagram were imported into STRING 11.0 and Cytoscape 3.8.0 for constructing the PPI network of the core targets,followed by GO and KEGG enrichment analysis using DAVID.Results:The new prescription consisted of sovereign medicinals Shengdi(生地),Xuanshen(玄参)and Maidong(麦冬)for Yangyin(养阴)and Shengjin(生津),minister medicinals Huangqi(黄芪)and Wuweizi(五味子)for Yiqi(益气)and Shengjin(生津),assistant medicinals Danshen(丹参)and Gegen(葛根)for Huoluo(活络)and Huayu(化瘀).All these Chinese medicinals together were effective for Yangyin(养阴),Yiqi(益气),Shengjin(生津),Huoxue(活血),Huayu(化瘀)and Tongluo(通络),thus enabling both the root cause and manifestations to be eliminated.It was extracted from numerous prescriptions and able to target the pathogenesis directly due to rational compatibility.The active components in this new prescription responsible for dealing with diabetic macroangiopathy wereβ-sitosterol,luteolin,tanshinone IIA,quercetin,etc.The core targets included MAPK8,EDN1,EGF,STAT3,PRKCA,EGFR,RELA,VEGFA,IL-6,PIK3 CA,AKT1,MAPK1,and TNF.The main signaling pathways were HIF-1,TNF,FoxO,VEGF,apoptosis,and osteoclast differentiation.Conclusion:Based on data mining and network pharmacology,this study has identified a new prescription capable of Yangyin(养阴),Yiqi(益气),Huoluo(活络)and Huayu(化瘀).It is able to target the pathogenesis of diabetic macroangiopathy due to Qiyin Liangxu(气阴两虚)and Xuemai Yuzu(血脉瘀阻)and prevent and control the diabetic macroangiopathy by regulating glucolipid metabolism,improving insulin resistance,relieving inflammation,and inhibiting oxidative stress response.This study has provided ideas for its future experimental research and clinical application.